# Prospective evaluation of outcomes in cirrhosis of different etiologies: impact of HIV infection and simvastatin therapy

> **NIH NIH U01** · CLEVELAND CLINIC LERNER COM-CWRU · 2024 · $733,101

## Abstract

Chronic liver disease, primarily cirrhosis, remains the 6th leading cause of death in adults younger than 65y in
the United States. Despite advances in diagnostics and therapies, mortality in cirrhosis has not changed
significantly over the last 40y and remains a major significant public health burden. We and others have used
modeling and database evaluations to show that alcohol related liver disease (ALD) and non-alcoholic fatty
liver disease (NAFLD) are the 2 major causes of cirrhosis in the United States. Treating the underlying etiology
of cirrhosis may help fibrosis regress but whether cirrhosis is reversible is not yet established. Whether fibrosis
progresses once a diagnosis of cirrhosis is established and if such a progression is related to decompensation
or hepatocellular carcinoma (HCC) are also not known. Of the various complications of cirrhosis, sarcopenia
and physical frailty due to impaired contractile function are frequent, progressive and adversely impact clinical
outcomes. Despite the high clinical significance, there are no prospective studies on development, progression
and predictors of sarcopenia and frailty in cirrhosis. Co-morbidities especially infection with human immune-
deficiency virus (HIV) places patients with cirrhosis at high risk of progression of fibrosis, decompensation, and
sarcopenia/frailty syndrome. The gut microbiome and their metabolites (xenometabolites) play a mechanistic
role in hepatic injury and complications of cirrhosis including HCC and sarcopenia but there are very limited
prospective studies in human patients. Most studies on the progression, long term complications, impact of co-
morbidities and outcomes in cirrhosis are cross-sectional, have small number of subjects, and do not translate
advances in mechanistic understanding of development of cirrhosis or its complications into clinical practice.
Therefore, prospective studies in well characterized cirrhosis are critical to develop effective management
strategies and improve outcomes. There is increasing interest in the use of statins in the management of
cirrhosis due to anti-inflammatory and antifibrotic effects that may prevent decompensation and HCC. The
Cleveland Clinic Health System is one of the largest clinical programs with a large population of patients with
cirrhosis who are referred for long-term management including liver transplantation, because of our expertise
in innovative approaches to patient care including televisits and applications of digital health incorporated into
integrated electronic medical records. In response to the RFA PAR DK-20-003, we propose to be a part of a
Liver Cirrhosis Network to establish a longitudinal cohort of patients with cirrhosis, primarily alcohol related and
non-alcoholic fatty liver disease with co-morbidities including HIV infection. We will develop a database of well
characterized patients and a biorepository from these patients to advance our mechanistic understanding of
progression of cir...

## Key facts

- **NIH application ID:** 10909240
- **Project number:** 5U01DK130180-04
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Srinivasan Dasarathy
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $733,101
- **Award type:** 5
- **Project period:** 2021-09-23 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909240

## Citation

> US National Institutes of Health, RePORTER application 10909240, Prospective evaluation of outcomes in cirrhosis of different etiologies: impact of HIV infection and simvastatin therapy (5U01DK130180-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10909240. Licensed CC0.

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